An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition

Charles E. Greif; R. Tyler Mertens; Gilles Berger; Sean Parkin; Samuel G. Awuah

doi:10.1039/d3cb00051f

An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition

Charles E. Greif, R. Tyler Mertens, Gilles Berger, Sean Parkin, Samuel G. Awuah

Research output: Contribution to journal › Article › peer-review

Abstract

Glioblastoma multiforme (GBM) is the most lethal brain cancer subtype, often advanced by the time of initial diagnosis. Existing treatment modalities including surgery, chemotherapy and radiation have been stymied by recurrence, metastasis, drug resistance and brain targetability. Here, we report a geometrically distinct Au(i) complex ligated by N^N-bidentate ligands and supported by a N-heterocyclic ligand that modulates mitochondrial morphology to inhibit GBM in vitro and in vivo. This work benefits from the facile preparation of anti-GBM Au(i)-NHC complexes.

Original language	English
Pages (from-to)	592-599
Number of pages	8
Journal	RSC Chemical Biology
Volume	4
Issue number	8
DOIs	https://doi.org/10.1039/d3cb00051f
State	Published - May 25 2023

Bibliographical note

Funding Information:
We thank all the core facilities at the University of Kentucky who provided support in completion of the experiments detailed in this manuscript. Specifically, the UK NMR Center supported by NSF (CHE-997738) and the flow cytometry and immune function core supported by the Office of the Vice President of Research, the Markey Cancer Center, and NCI Center Core Support Grant (P30 CA177558), and the microscopy facilities (UK Light Microscopy Core) for their assistance. We thank Dr. Tomoko Sengoku and Mr. Michael Alstott for their support with our redox metabolism experiments, supported by the shared resource(s) of the University of Kentucky Markey Cancer Center (P30CA177558). This work was funded by National Institutes of Health/NCI grant R01CA258421-01 (S. G. A.).

Publisher Copyright:
© 2023 RSC.

ASJC Scopus subject areas

Chemistry (miscellaneous)
Biochemistry
Molecular Biology
Biochemistry, Genetics and Molecular Biology (miscellaneous)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/d3cb00051f

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title = "An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition",

abstract = "Glioblastoma multiforme (GBM) is the most lethal brain cancer subtype, often advanced by the time of initial diagnosis. Existing treatment modalities including surgery, chemotherapy and radiation have been stymied by recurrence, metastasis, drug resistance and brain targetability. Here, we report a geometrically distinct Au(i) complex ligated by N^N-bidentate ligands and supported by a N-heterocyclic ligand that modulates mitochondrial morphology to inhibit GBM in vitro and in vivo. This work benefits from the facile preparation of anti-GBM Au(i)-NHC complexes.",

author = "Greif, {Charles E.} and Mertens, {R. Tyler} and Gilles Berger and Sean Parkin and Awuah, {Samuel G.}",

note = "Funding Information: We thank all the core facilities at the University of Kentucky who provided support in completion of the experiments detailed in this manuscript. Specifically, the UK NMR Center supported by NSF (CHE-997738) and the flow cytometry and immune function core supported by the Office of the Vice President of Research, the Markey Cancer Center, and NCI Center Core Support Grant (P30 CA177558), and the microscopy facilities (UK Light Microscopy Core) for their assistance. We thank Dr. Tomoko Sengoku and Mr. Michael Alstott for their support with our redox metabolism experiments, supported by the shared resource(s) of the University of Kentucky Markey Cancer Center (P30CA177558). This work was funded by National Institutes of Health/NCI grant R01CA258421-01 (S. G. A.). Publisher Copyright: {\textcopyright} 2023 RSC.",

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AU - Greif, Charles E.

AU - Mertens, R. Tyler

AU - Berger, Gilles

AU - Parkin, Sean

AU - Awuah, Samuel G.

N1 - Funding Information: We thank all the core facilities at the University of Kentucky who provided support in completion of the experiments detailed in this manuscript. Specifically, the UK NMR Center supported by NSF (CHE-997738) and the flow cytometry and immune function core supported by the Office of the Vice President of Research, the Markey Cancer Center, and NCI Center Core Support Grant (P30 CA177558), and the microscopy facilities (UK Light Microscopy Core) for their assistance. We thank Dr. Tomoko Sengoku and Mr. Michael Alstott for their support with our redox metabolism experiments, supported by the shared resource(s) of the University of Kentucky Markey Cancer Center (P30CA177558). This work was funded by National Institutes of Health/NCI grant R01CA258421-01 (S. G. A.). Publisher Copyright: © 2023 RSC.

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N2 - Glioblastoma multiforme (GBM) is the most lethal brain cancer subtype, often advanced by the time of initial diagnosis. Existing treatment modalities including surgery, chemotherapy and radiation have been stymied by recurrence, metastasis, drug resistance and brain targetability. Here, we report a geometrically distinct Au(i) complex ligated by N^N-bidentate ligands and supported by a N-heterocyclic ligand that modulates mitochondrial morphology to inhibit GBM in vitro and in vivo. This work benefits from the facile preparation of anti-GBM Au(i)-NHC complexes.

AB - Glioblastoma multiforme (GBM) is the most lethal brain cancer subtype, often advanced by the time of initial diagnosis. Existing treatment modalities including surgery, chemotherapy and radiation have been stymied by recurrence, metastasis, drug resistance and brain targetability. Here, we report a geometrically distinct Au(i) complex ligated by N^N-bidentate ligands and supported by a N-heterocyclic ligand that modulates mitochondrial morphology to inhibit GBM in vitro and in vivo. This work benefits from the facile preparation of anti-GBM Au(i)-NHC complexes.

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An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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